Project Grant R21HL188689

The National Heart, Lung, and Blood Institute awarded Yale University $313,649 under the Cardiovascular Diseases Research program (CFDA 93.837) on August 15, 2026, to derive and validate a clinical prediction rule identifying febrile children and adolescents with sickle cell disease at low risk for bacteremia.

The project addresses overtreatment of febrile children with sickle cell disease in emergency departments. Existing clinical guidelines recommend aggressive evaluation for bacteremia due to the 1–2% bacteremia risk posed by reduced or absent splenic function in this population. Current practice results in over 90% of febrile children with sickle cell disease receiving empirical parenteral antibiotic therapy, typically ceftriaxone, and more than 50% undergoing hospitalization while awaiting blood culture results. This management strategy carries iatrogenic risks, including potentially fatal acute hemolysis with ceftriaxone and emerging antibiotic resistance. Prior studies attempting to identify bacteremia predictors have suffered from limitations including single-center designs, small sample sizes, reliance on administrative data, and insufficient discriminatory ability. The award will support derivation and validation of a prediction rule using objective demographic, patient history, clinical, and laboratory data across a multicenter sample, employing robust statistical techniques to create an evidence-based risk stratification tool translatable to clinical practice.

Performance occurs in New Haven, Connecticut. The award period runs through May 31, 2028.